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2. Genomic characterization of DICER1-associated neoplasms uncovers molecular classes.

Author

Kommoss, F.K.F., Chong, A.S., Chong, A.L., Pfaff, E., Jones, D.T.W., Hiemcke-Jiwa, L.S., Kester, L.A., Flucke, U.E., Gessler, M., Schrimpf, D., Sahm, F., Clarke, B.A., Stewart, C.J.R., Wang, Yemin, Gilks, C.B., Kommoss, F., Huntsman, D.G., Schüller, U., Koelsche, C., Glenn McCluggage, W., Deimling, A. von, Foulkes, W.D., Kommoss, F.K.F., Chong, A.S., Chong, A.L., Pfaff, E., Jones, D.T.W., Hiemcke-Jiwa, L.S., Kester, L.A., Flucke, U.E., Gessler, M., Schrimpf, D., Sahm, F., Clarke, B.A., Stewart, C.J.R., Wang, Yemin, Gilks, C.B., Kommoss, F., Huntsman, D.G., Schüller, U., Koelsche, C., Glenn McCluggage, W., Deimling, A. von, and Foulkes, W.D.

Abstract

Item does not contain fulltext, DICER1 syndrome is a tumor predisposition syndrome that is associated with up to 30 different neoplastic lesions, usually affecting children and adolescents. Here we identify a group of mesenchymal tumors which is highly associated with DICER1 syndrome, and molecularly distinct from other DICER1-associated tumors. This group of DICER1-associated mesenchymal tumors encompasses multiple well-established clinicopathological tumor entities and can be further divided into three clinically meaningful classes designated "low-grade mesenchymal tumor with DICER1 alteration" (LGMT DICER1), "sarcoma with DICER1 alteration" (SARC DICER1), and primary intracranial sarcoma with DICER1 alteration (PIS DICER1). Our study not only provides a combined approach to classify DICER1-associated neoplasms for improved clinical management but also suggests a role for global hypomethylation and other recurrent molecular events in sarcomatous differentiation in mesenchymal tumors with DICER1 alteration. Our results will facilitate future investigations into prognostication and therapeutic approaches for affected patients.

Published
2023

3. Clinical characteristics and clinical evolution of a large cohort of pediatric patients with primary central nervous system (cns) tumors and tropomyosin receptor kinase (trk) fusion.

Author

Lamoureux A.-A., Fisher M., Lemelle L., Pfaff E., Kramm C., De Wilde B., Kazanowska B., Hutter C., Pfister S.M., Sturm D., Jones D., Orbach D., Pierron G., Raskin S., Drilon A., Diamond E., Harada G., Zapotocky M., Ellezam B., Weil A.G., Venne D., Barritault M., Leblond P., Coltin H., Hammad R., Tabori U., Hawkins C., Hansford J.R., Meyran D., Erker C., McFadden K., Sato M., Gottardo N.G., Dholaria H., Noroxe D.S., Goto H., Ziegler D.S., Lin F.Y., Parsons D.W., Lindsay H., Wong T.-T., Liu Y.-L., Wu K.-S., Franson A.F., Hwang E., Aguilar-Bonilla A., Cheng S., Cacciotti C., Massimino M., Schiavello E., Wood P., Hoffman L.M., Cappellano A., Lassaletta A., Van Damme A., Llort A., Gerber N.U., Ceruso M.S., Bendel A.E., Skrypek M., Hamideh D., Mushtaq N., Walter A., Jabado N., Alsahlawi A., Farmer J.-P., Abadi C.C., Mueller S., Mazewski C., Aguilera D., Robison N., O'Halloran K., Abbou S., Berlanga P., Geoerger B., Ora I., Moertel C.L., Razis E.D., Vernadou A., Doz F., Laetsch T.W., Perreault S., Lamoureux A.-A., Fisher M., Lemelle L., Pfaff E., Kramm C., De Wilde B., Kazanowska B., Hutter C., Pfister S.M., Sturm D., Jones D., Orbach D., Pierron G., Raskin S., Drilon A., Diamond E., Harada G., Zapotocky M., Ellezam B., Weil A.G., Venne D., Barritault M., Leblond P., Coltin H., Hammad R., Tabori U., Hawkins C., Hansford J.R., Meyran D., Erker C., McFadden K., Sato M., Gottardo N.G., Dholaria H., Noroxe D.S., Goto H., Ziegler D.S., Lin F.Y., Parsons D.W., Lindsay H., Wong T.-T., Liu Y.-L., Wu K.-S., Franson A.F., Hwang E., Aguilar-Bonilla A., Cheng S., Cacciotti C., Massimino M., Schiavello E., Wood P., Hoffman L.M., Cappellano A., Lassaletta A., Van Damme A., Llort A., Gerber N.U., Ceruso M.S., Bendel A.E., Skrypek M., Hamideh D., Mushtaq N., Walter A., Jabado N., Alsahlawi A., Farmer J.-P., Abadi C.C., Mueller S., Mazewski C., Aguilera D., Robison N., O'Halloran K., Abbou S., Berlanga P., Geoerger B., Ora I., Moertel C.L., Razis E.D., Vernadou A., Doz F., Laetsch T.W., and Perreault S.

Abstract

BACKGROUND: TRK fusions are detected in less than 3% of CNS tumors. Given their rarity, there are limited data on the clinical course of these patients. METHOD(S): We contacted 166 oncology centers worldwide to retrieve data on patients with TRK fusion-driven CNS tumors. Data extracted included demographics, histopathology, NTRK gene fusion, treatment modalities and outcomes. Patients less than 18 years of age at diagnosis were included in this analysis. RESULT(S): Seventy-three pediatric patients with TRK fusion-driven primary CNS tumors were identified. Median age at diagnosis was 2.4 years (range 0.0-17.8) and 60.2 % were male. NTRK2 gene fusions were found in 37 patients (50.7%), NTRK1 and NTRK3 aberrations were detected in 19 (26.0%) and 17 (23.3%), respectively. Tumor types included 38 high-grade gliomas (HGG; 52.1%), 20 low-grade gliomas (LGG; 27.4%), 4 embryonal tumors (5.5%) and 11 others (15.1%). Median follow-up was 46.5 months (range 3-226). During the course of their disease, a total of 62 (84.9%) patients underwent surgery with a treatment intent, 50 (68.5%) patients received chemotherapy, 35 (47.9%) patients received radiation therapy, while 34 (46.6%) patients received NTRK inhibitors (3 as first line treatment). Twenty-four (32.9%) had no progression including 9 LGG (45%) and 9 HGG (23.6%). At last follow-up, only one (5.6%-18 evaluable) patient with LGG died compared to 11 with HGG (35.5%-31 evaluable). For LGG the median progression-free survival (PFS) after the first line of treatment was 17 months (95% CI: 0.0-35.5) and median overall survival (OS) was not reached. For patients with HGG the median PFS was 30 months (95% CI: 11.9-48.1) and median OS was 182 months (95% CI 20.2-343.8). CONCLUSION(S): We report the largest cohort of pediatric patients with TRK fusion-driven primary CNS tumors. These results will help us to better understand clinical evolution and compare outcomes with ongoing clinical trials.

Published
2022

4. HGG-11. Clinical characteristics and clinical evolution of a large cohort of pediatric patients with primary central nervous system (CNS) tumors and tropomyosin receptor kinase (TRK) fusion.

Author

Lamoureux, A-A, Fisher, M, Lemelle, L, Pfaff, E, Kramm, C, De Wilde, B, Kazanowska, B, Hutter, C, Pfister, SM, Sturm, D, Jones, D, Orbach, D, Pierron, G, Raskin, S, Drilon, A, Diamond, E, Harada, G, Zapotocky, M, Ellezam, B, Weil, AG, Venne, D, Barritault, M, Leblond, P, Coltin, H, Hammad, R, Tabori, U, Hawkins, C, Hansford, JR, Meyran, D, Erker, C, McFadden, K, Sato, M, Gottardo, NG, Dholaria, H, Nørøxe, DS, Goto, H, Ziegler, DS, Lin, FY, Parsons, DW, Lindsay, H, Wong, T-T, Liu, Y-L, Wu, K-S, Franson, AF, Hwang, E, Aguilar-Bonilla, A, Cheng, S, Cacciotti, C, Massimino, M, Schiavello, E, Wood, P, Hoffman, LM, Cappellano, A, Lassaletta, A, Van Damme, A, Llort, A, Gerber, NU, Ceruso, MS, Bendel, AE, Skrypek, M, Hamideh, D, Mushtaq, N, Walter, A, Jabado, N, Alsahlawi, A, Farmer, J-P, Abadi, CC, Mueller, S, Mazewski, C, Aguilera, D, Robison, N, O’Halloran, K, Abbou, S, Berlanga, P, Geoerger, B, Øra, I, Moertel, CL, Razis, ED, Vernadou, A, Doz, F, Laetsch, TW, Perreault, S, Lamoureux, A-A, Fisher, M, Lemelle, L, Pfaff, E, Kramm, C, De Wilde, B, Kazanowska, B, Hutter, C, Pfister, SM, Sturm, D, Jones, D, Orbach, D, Pierron, G, Raskin, S, Drilon, A, Diamond, E, Harada, G, Zapotocky, M, Ellezam, B, Weil, AG, Venne, D, Barritault, M, Leblond, P, Coltin, H, Hammad, R, Tabori, U, Hawkins, C, Hansford, JR, Meyran, D, Erker, C, McFadden, K, Sato, M, Gottardo, NG, Dholaria, H, Nørøxe, DS, Goto, H, Ziegler, DS, Lin, FY, Parsons, DW, Lindsay, H, Wong, T-T, Liu, Y-L, Wu, K-S, Franson, AF, Hwang, E, Aguilar-Bonilla, A, Cheng, S, Cacciotti, C, Massimino, M, Schiavello, E, Wood, P, Hoffman, LM, Cappellano, A, Lassaletta, A, Van Damme, A, Llort, A, Gerber, NU, Ceruso, MS, Bendel, AE, Skrypek, M, Hamideh, D, Mushtaq, N, Walter, A, Jabado, N, Alsahlawi, A, Farmer, J-P, Abadi, CC, Mueller, S, Mazewski, C, Aguilera, D, Robison, N, O’Halloran, K, Abbou, S, Berlanga, P, Geoerger, B, Øra, I, Moertel, CL, Razis, ED, Vernadou, A, Doz, F, Laetsch, TW, and Perreault, S

Abstract

BACKGROUND: TRK fusions are detected in less than 3% of CNS tumors. Given their rarity, there are limited data on the clinical course of these patients. METHODS: We contacted 166 oncology centers worldwide to retrieve data on patients with TRK fusion-driven CNS tumors. Data extracted included demographics, histopathology, NTRK gene fusion, treatment modalities and outcomes. Patients less than 18 years of age at diagnosis were included in this analysis. RESULTS: Seventy-three pediatric patients with TRK fusion-driven primary CNS tumors were identified. Median age at diagnosis was 2.4 years (range 0.0–17.8) and 60.2 % were male. NTRK2 gene fusions were found in 37 patients (50.7%), NTRK1 and NTRK3 aberrations were detected in 19 (26.0%) and 17 (23.3%), respectively. Tumor types included 38 high-grade gliomas (HGG; 52.1%), 20 low-grade gliomas (LGG; 27.4%), 4 embryonal tumors (5.5%) and 11 others (15.1%). Median follow-up was 46.5 months (range 3-226). During the course of their disease, a total of 62 (84.9%) patients underwent surgery with a treatment intent, 50 (68.5%) patients received chemotherapy, 35 (47.9%) patients received radiation therapy, while 34 (46.6%) patients received NTRK inhibitors (3 as first line treatment). Twenty-four (32.9%) had no progression including 9 LGG (45%) and 9 HGG (23.6%). At last follow-up, only one (5.6%-18 evaluable) patient with LGG died compared to 11 with HGG (35.5%-31 evaluable). For LGG the median progression-free survival (PFS) after the first line of treatment was 17 months (95% CI: 0.0-35.5) and median overall survival (OS) was not reached. For patients with HGG the median PFS was 30 months (95% CI: 11.9-48.1) and median OS was 182 months (95% CI 20.2-343.8). CONCLUSIONS: We report the largest cohort of pediatric patients with TRK fusion-driven primary CNS tumors. These results will help us to better understand clinical evolution and compare outcomes with ongoing clinical trials.

Published
2022

16. Brainstem biopsy in paediatric diffuse intrinsic pontine glioma in the era of precision medicine – the INFORM study experience

Author

El Damaty, A, Pfaff, E, Kiening, K, Unterberg, AW, Witt, O, and Bächli, H

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Objective: Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brain tumor with fatal outcome. The INFORM registry offers comprehensive molecular profiling of high-risk tumors in order to identify target alterations for potential precision therapy. We analyzed molecular characteristics[for full text, please go to the a.m. URL], 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Published
2019
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21. Optimizing research in symptomatic uterine fibroids with development of a computable phenotype for use with electronic health records

Author

Schiff, L., Westreich, D., Nicholson, W.K., Pfaff, E., Vines, A.I., Hoffman, S.R., Johnson, L.-S., Sundaresan, A., and Halladay, J.R.

Subjects
female genital diseases and pregnancy complications
Abstract

Background: Women with symptomatic uterine fibroids can report a myriad of symptoms, including pain, bleeding, infertility, and psychosocial sequelae. Optimizing fibroid research requires the ability to enroll populations of women with image-confirmed symptomatic uterine fibroids. Objective: Our objective was to develop an electronic health record–based algorithm to identify women with symptomatic uterine fibroids for a comparative effectiveness study of medical or surgical treatments on quality-of-life measures. Using an iterative process and text-mining techniques, an effective computable phenotype algorithm, composed of demographics, and clinical and laboratory characteristics, was developed with reasonable performance. Such algorithms provide a feasible, efficient way to identify populations of women with symptomatic uterine fibroids for the conduct of large traditional or pragmatic trials and observational comparative effectiveness studies. Symptomatic uterine fibroids, due to menorrhagia, pelvic pain, bulk symptoms, or infertility, are a source of substantial morbidity for reproductive-age women. Comparing Treatment Options for Uterine Fibroids is a multisite registry study to compare the effectiveness of hormonal or surgical fibroid treatments on women's perceptions of their quality of life. Electronic health record–based algorithms are able to identify large numbers of women with fibroids, but additional work is needed to develop electronic health record algorithms that can identify women with symptomatic fibroids to optimize fibroid research. We sought to develop an efficient electronic health record–based algorithm that can identify women with symptomatic uterine fibroids in a large health care system for recruitment into large-scale observational and interventional research in fibroid management. Study Design: We developed and assessed the accuracy of 3 algorithms to identify patients with symptomatic fibroids using an iterative approach. The data source was the Carolina Data Warehouse for Health, a repository for the health system's electronic health record data. In addition to International Classification of Diseases, Ninth Revision diagnosis and procedure codes and clinical characteristics, text data–mining software was used to derive information from imaging reports to confirm the presence of uterine fibroids. Results of each algorithm were compared with expert manual review to calculate the positive predictive values for each algorithm. Results: Algorithm 1 was composed of the following criteria: (1) age 18-54 years; (2) either ≥1 International Classification of Diseases, Ninth Revision diagnosis codes for uterine fibroids or mention of fibroids using text-mined key words in imaging records or documents; and (3) no International Classification of Diseases, Ninth Revision or Current Procedural Terminology codes for hysterectomy and no reported history of hysterectomy. The positive predictive value was 47% (95% confidence interval 39–56%). Algorithm 2 required ≥2 International Classification of Diseases, Ninth Revision diagnosis codes for fibroids and positive text-mined key words and had a positive predictive value of 65% (95% confidence interval 50–79%). In algorithm 3, further refinements included ≥2 International Classification of Diseases, Ninth Revision diagnosis codes for fibroids on separate outpatient visit dates, the exclusion of women who had a positive pregnancy test within 3 months of their fibroid-related visit, and exclusion of incidentally detected fibroids during prenatal or emergency department visits. Algorithm 3 achieved a positive predictive value of 76% (95% confidence interval 71–81%). Conclusion: An electronic health record–based algorithm is capable of identifying cases of symptomatic uterine fibroids with moderate positive predictive value and may be an efficient approach for large-scale study recruitment.

Published
2018
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24. Molecular Characterization of Radiation-induced Glioblastoma

Author

Deng, MY, additional, Sturm, D, additional, Pfaff, E, additional, Balasubrama, GP, additional, Schittenhelm, J, additional, Ebinger, M, additional, Schuhmann, M, additional, Korshunov, A, additional, Deimling, A, additional, Witt, O, additional, Pfister, SM, additional, and Jones, DTW, additional

Published
2018
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26. Properties of the myc-Gene Product: Nuclear Association, Inhibition of Transcription and Activation in Stimulated Lymphocytes

Author

Moelling, K., Benter, T., Bunte, T., Pfaff, E., Deppert, W., Egly, J. M., Miyamoto, N. B., Cooper, M., editor, Goebel, W., editor, Hofschneider, P. H., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Rott, R., editor, Schweiger, H. G., editor, Vogt, P. K., editor, Zinkernagel, R., editor, Potter, Michael, editor, Melchers, Fritz, editor, and Weigert, Martin, editor

Published
1984
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29. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Author

Sturm, D., Orr, B.A., Toprak, U.H., Hovestadt, V., Jones, D.T., Capper, D., Sill, M., Buchhalter, I., Northcott, P.A., Leis, I., Ryzhova, M., Koelsche, C., Pfaff, E., Allen, S.J., Balasubramanian, G., Worst, B.C., Pajtler, K.W., Brabetz, S., Johann, P.D., Sahm, F., Reimand, J., Mackay, A., Carvalho, D.M., Remke, M., Phillips, J.J., Perry, A., Cowdrey, C., Drissi, R., Fouladi, M., Giangaspero, F., Lastowska, M., Grajkowska, W., Scheurlen, W., Pietsch, T., Hagel, C., Gojo, J., Lotsch, D., Berger, W., Slavc, I., Haberler, C., Jouvet, A., Holm, S., Hofer, S., Prinz, M., Keohane, C., Fried, I., Mawrin, C., Scheie, D., Mobley, B.C., Schniederjan, M.J., Santi, M., Buccoliero, A.M., Dahiya, S., Kramm, C.M., Bueren, A.O. von, Hoff, K. von, Rutkowski, S., Herold-Mende, C., Fruhwald, M.C., Milde, T., Hasselblatt, M., Wesseling, P., Rossler, J., Schuller, U., Ebinger, M., Schittenhelm, J., Frank, S., Grobholz, R., Vajtai, I., Hans, V., Schneppenheim, R., Zitterbart, K., Collins, V.P., Aronica, E., Varlet, P., Puget, S., Dufour, C., Grill, J., Figarella-Branger, D., Wolter, M., Schuhmann, M.U., Shalaby, T., Grotzer, M., Meter, T. van, Monoranu, C.M., Felsberg, J., Reifenberger, G., Snuderl, M., Forrester, L.A., Koster, J., Versteeg, R., Volckmann, R., Sluis, P. van, Wolf, S., Mikkelsen, T., Gajjar, A., Aldape, K., Moore, A.S., Taylor, M.D., Jones, C., et al., Sturm, D., Orr, B.A., Toprak, U.H., Hovestadt, V., Jones, D.T., Capper, D., Sill, M., Buchhalter, I., Northcott, P.A., Leis, I., Ryzhova, M., Koelsche, C., Pfaff, E., Allen, S.J., Balasubramanian, G., Worst, B.C., Pajtler, K.W., Brabetz, S., Johann, P.D., Sahm, F., Reimand, J., Mackay, A., Carvalho, D.M., Remke, M., Phillips, J.J., Perry, A., Cowdrey, C., Drissi, R., Fouladi, M., Giangaspero, F., Lastowska, M., Grajkowska, W., Scheurlen, W., Pietsch, T., Hagel, C., Gojo, J., Lotsch, D., Berger, W., Slavc, I., Haberler, C., Jouvet, A., Holm, S., Hofer, S., Prinz, M., Keohane, C., Fried, I., Mawrin, C., Scheie, D., Mobley, B.C., Schniederjan, M.J., Santi, M., Buccoliero, A.M., Dahiya, S., Kramm, C.M., Bueren, A.O. von, Hoff, K. von, Rutkowski, S., Herold-Mende, C., Fruhwald, M.C., Milde, T., Hasselblatt, M., Wesseling, P., Rossler, J., Schuller, U., Ebinger, M., Schittenhelm, J., Frank, S., Grobholz, R., Vajtai, I., Hans, V., Schneppenheim, R., Zitterbart, K., Collins, V.P., Aronica, E., Varlet, P., Puget, S., Dufour, C., Grill, J., Figarella-Branger, D., Wolter, M., Schuhmann, M.U., Shalaby, T., Grotzer, M., Meter, T. van, Monoranu, C.M., Felsberg, J., Reifenberger, G., Snuderl, M., Forrester, L.A., Koster, J., Versteeg, R., Volckmann, R., Sluis, P. van, Wolf, S., Mikkelsen, T., Gajjar, A., Aldape, K., Moore, A.S., Taylor, M.D., Jones, C., and et al.

Abstract

Item does not contain fulltext, Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

Published
2016

34. Manufacturing experience of beam dump for SPIDER facility

Author

Patel, H., primary, Rotti, C., additional, Nagaraju, M.V., additional, Chakraborty, A., additional, Schunke, B., additional, Chareyre, J., additional, Boilson, D., additional, Svensson, L., additional, Palma, M.Dalla, additional, Zaccaria, P., additional, Pasqualotto, R., additional, Pfaff, E., additional, Schafer, J., additional, and Eckardt, C., additional

Published
2015
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35. WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma

Author

Zhukova, N, Ramaswamy, V, Remke, M, Martin, DC, Castelo-Branco, P, Zhang, CH, Fraser, M, Tse, K, Poon, R, Shih, DJH, Baskin, B, Ray, PN, Bouffet, E, Dirks, P, von Bueren, AO, Pfaff, E, Korshunov, A, Jones, DTW, Northcott, PA, Kool, M, Pugh, TJ, Pomeroy, SL, Cho, YJ, Pietsch, T, Gessi, M, Rutkowski, S, Bognár, L, Cho, BK, Eberhart, CG, Conter, CF, Fouladi, M, French, PJ, Grajkowska, WA, Gupta, N, Hauser, P, Jabado, N, Vasiljevic, A, Jung, S, Kim, SK, Klekner, A, Kumabe, T, Lach, B, Leonard, JR, Liau, LM, Massimi, L, Pollack, IF, Ra, YS, Rubin, JB, Van Meir, EG, Wang, KC, Weiss, WA, Zitterbart, K, Bristow, RG, Alman, B, Hawkins, CE, Malkin, D, Clifford, SC, Pfister, SM, Taylor, MD, Tabori, U, Zhukova, N, Ramaswamy, V, Remke, M, Martin, DC, Castelo-Branco, P, Zhang, CH, Fraser, M, Tse, K, Poon, R, Shih, DJH, Baskin, B, Ray, PN, Bouffet, E, Dirks, P, von Bueren, AO, Pfaff, E, Korshunov, A, Jones, DTW, Northcott, PA, Kool, M, Pugh, TJ, Pomeroy, SL, Cho, YJ, Pietsch, T, Gessi, M, Rutkowski, S, Bognár, L, Cho, BK, Eberhart, CG, Conter, CF, Fouladi, M, French, PJ, Grajkowska, WA, Gupta, N, Hauser, P, Jabado, N, Vasiljevic, A, Jung, S, Kim, SK, Klekner, A, Kumabe, T, Lach, B, Leonard, JR, Liau, LM, Massimi, L, Pollack, IF, Ra, YS, Rubin, JB, Van Meir, EG, Wang, KC, Weiss, WA, Zitterbart, K, Bristow, RG, Alman, B, Hawkins, CE, Malkin, D, Clifford, SC, Pfister, SM, Taylor, MD, and Tabori, U

Abstract

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6% ± 8.7%, respectively (p < 0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% ± 2% vs. 57.4% ± 1.8% (p < 0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5% ± 1.5% in lithium treated cells vs. 56.6 ± 3% (p < 0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% ± 8% for lithium treated cells vs. 27% ± 3% for untreated controls (p = 0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

Published
2014

36. Animals and Medicines

Author

Collins, J., primary, Betz, H., additional, Rowlands, D. J., additional, Davies, J. E., additional, Schaller, H., additional, Fiers, W., additional, Siewert, G., additional, Paoletti, E., additional, Sippel, A. E., additional, Pfaff, E., additional, and Wagner, E. F., additional

Published
1986
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40. [Phenotypic and functional characterization of porcine T-lymphocytes]

Author

Armin Saalmüller, Pauly T, and Pfaff E

Subjects
Antigens, Differentiation, T-Lymphocyte, CD4-Positive T-Lymphocytes, Swine, T-Lymphocytes, Animals, CD8-Positive T-Lymphocytes, Immunophenotyping
Abstract

Monoclonal antibodies (mAb) against leucocyte differentiation antigens have altered the way in which immunologists examine the immune system. These mAb allow to identify distinct surface molecules on leukocyte populations, by which these cells can be classified, isolated and studied for their functional properties. This review summarises the knowledge about differentiation antigens useful in the characterisation of porcine T-lymphocytes. Furthermore it focuses on several properties of porcine T-lymphocytes and T-lymphocyte subpopulations.

Published
1998

43. EPENDYMOMA

Author

Zaghloul, M., primary, Elbeltagy, M., additional, Mousa, A., additional, Eldebawy, E., additional, Amin, A., additional, Pavelka, Z., additional, Vranova, V., additional, Valaskova, I., additional, Tomasikova, L., additional, Oltova, A., additional, Ventruba, J., additional, Mackerle, Z., additional, Kren, L., additional, Skotakova, J., additional, Zitterbart, K., additional, Sterba, J., additional, Milde, T., additional, Kleber, S., additional, Korshunov, A., additional, Witt, H., additional, Hielscher, T., additional, Koch, P., additional, Koch, H.-G., additional, Jugold, M., additional, Deubzer, H. E., additional, Oehme, I., additional, Lodrini, M., additional, Grone, H.-J., additional, Benner, A., additional, Brustle, O., additional, Gilbertson, R. J., additional, von Deimling, A., additional, Kulozik, A. E., additional, Pfister, S. M., additional, Ana, M.-V., additional, Witt, O., additional, Kool, M., additional, Mack, S. C., additional, Taylor, M. D., additional, Fouyssac, F., additional, Schmitt, E., additional, Mansuy, L., additional, Marchal, J.-C., additional, Coffinet, L., additional, Bernier, V., additional, Chastagner, P., additional, Sperl, D., additional, Zacharoulis, S., additional, Massimino, M., additional, Schiavello, E., additional, Pizer, B., additional, Piette, C., additional, Kitanovski, L., additional, von Hoff, K., additional, Quehenberger, F., additional, Rutkowski, S., additional, Benesch, M., additional, Tzaridis, T.-D., additional, Bender, S., additional, Pfaff, E., additional, Barbus, S., additional, Bageritz, J., additional, Jones, D.-T.-W., additional, Kulozik, A., additional, Lichter, P., additional, Pfister, S.-M., additional, Song, S.-H., additional, Kang, C.-W., additional, Kim, S.-H., additional, Bandopadhayay, P., additional, Ullrich, N., additional, Goumnerova, L., additional, Scott, R. M., additional, Silvera, V. M., additional, Ligon, K. L., additional, Marcus, K. J., additional, Robison, N., additional, Manley, P. E., additional, Chi, S., additional, Kieran, M. W., additional, Biassoni, V., additional, Pierani, P., additional, Cesaro, S., additional, Maura, M., additional, Mack, S., additional, Jager, N., additional, Jones, D. T. W., additional, Stutz, A., additional, Northcott, P. A., additional, Fults, D. W., additional, Gupta, N., additional, Karajannis, M., additional, Rutka, J. T., additional, Korbel, J., additional, de Rezende, A. C. P., additional, Chen, M. J., additional, da Silva, N. S., additional, Cappellano, A., additional, Cavalheiro, S., additional, Weltman, E., additional, Currle, S., additional, Thiruvenkatam, R., additional, Murugesan, M., additional, Kranenburg, T., additional, Phoenix, T., additional, Gupta, K., additional, Gilbertson, R., additional, Rogers, H., additional, Kilday, J.-P., additional, Mayne, C., additional, Ward, J., additional, Adamowicz-Brice, M., additional, Schwalbe, E., additional, Clifford, S., additional, Coyle, B., additional, Grundy, R., additional, Mitra, B., additional, Domerg, C., additional, Andreiuolo, F., additional, Osteso-Ibanez, T., additional, Mauguen, A., additional, Varlet, P., additional, Le Deley, M.-C., additional, Lowe, J., additional, Ellison, D. W., additional, Grill, J., additional, Grundy, R. G., additional, Fleischhack, G., additional, Pajtler, K., additional, Zimmermann, M., additional, Warmuth-Metz, M., additional, Kortmann, R.-D., additional, Pietsch, T., additional, Faldum, A., additional, Bode, U., additional, Gandola, L., additional, Pecori, E., additional, Scarzello, G., additional, Barra, S., additional, Mascarin, M., additional, Scoccianti, S., additional, Mussano, A., additional, Garre, M. L., additional, Jacopo, S., additional, Viscardi, E., additional, Balter, R., additional, Bertin, D., additional, Giangaspero, F., additional, Pearlman, M., additional, Khatua, S., additional, Van Meter, T., additional, Koul, D., additional, Yung, A., additional, Paulino, A., additional, Su, J., additional, Dauser, R., additional, Whitehead, W., additional, Teh, B., additional, Chintagumpala, M., additional, Perek, D., additional, Drogosiewicz, M., additional, Filipek, I., additional, Polnik, M. P., additional, Baginska, B. D., additional, Wachowiak, J., additional, Kazmierczak, B., additional, Sobol, G., additional, Musiol, K., additional, Kowalczyk, J., additional, Slusarz, H. W., additional, Peregud-Pogorzelski, J., additional, Grajkowska, W., additional, Roszkowski, M., additional, Teo, W.-Y., additional, Okcu, F., additional, Mahajan, A., additional, Adesina, A., additional, Jea, A., additional, Bollo, R., additional, Paulino, A. C., additional, Velez-Char, N., additional, Doerner, E., additional, Muehlen, A. z., additional, Vladimirova, V., additional, Kortmann, R., additional, Friedrich, C., additional, von Bueren, A. O., additional, Barszczyk, M., additional, Buczkowicz, P., additional, Morrison, A., additional, Tabori, U., additional, Hawkins, C., additional, Krajewski, K., additional, Kammler, G., additional, von Bueren, A., additional, Krauss, J., additional, Ferreira, C., additional, Dieffenbach, G., additional, Barbosa, C., additional, Cuny, P., additional, Piccinin, E., additional, Brenca, M., additional, Lorenzetto, E., additional, Sardi, I., additional, Genitori, L., additional, Pollo, B., additional, Maestro, R., additional, Modena, P., additional, MacDonald, S., additional, Ebb, D., additional, Lavally, B., additional, Yeap, B., additional, Marcus, K., additional, Tarbell, N., additional, Yock, T., additional, Schittone, S., additional, Donson, A., additional, Birks, D., additional, Amani, V., additional, Griesinger, A., additional, Handler, M., additional, Madey, M., additional, Merchant, T., additional, Foreman, N., additional, Hukin, J., additional, Ailon, T., additional, Dunham, C., additional, Carret, A.-S., additional, McNeely, P. D., additional, Zelcer, S., additional, Wilson, B., additional, Lafay-Cousin, L., additional, Johnston, D., additional, Eisenstat, D., additional, Silva, M., additional, Jabado, N., additional, Yip, S., additional, Goddard, K., additional, Fryer, C., additional, Hendson, G., additional, Dunn, S., additional, Singhal, A., additional, Lassen-Ramshad, Y., additional, Vestergaard, A., additional, Seiersen, K., additional, Schultz, H. P., additional, Hoeyer, M., additional, Petersen, J. B., additional, Moreno, L., additional, Popov, S., additional, Jury, A., additional, Al Sarraj, S., additional, Jones, C., additional, Bowers, D., additional, Gargan, L., additional, Horton, C. J., additional, Rakheja, D., additional, Margraf, L., additional, Yeung, J., additional, Hamilton, R., additional, Okada, H., additional, Jakacki, R., additional, Pollack, I., additional, Fleming, A., additional, Saint-Martin, C., additional, Freeman, C., additional, Albrecht, S., additional, and Montes, J.-L., additional

Published
2012
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44. HIGH GRADE GLIOMAS

Author

Leonard, A., primary, Wolff, J., additional, Sengupta, R., additional, Marassa, J., additional, Piwnica-Worms, D., additional, Rubin, J., additional, Pollack, I., additional, Jakacki, R., additional, Butterfield, L., additional, Okada, H., additional, Fangusaro, J., additional, Warren, K. E., additional, Mullins, C., additional, Jurgen, P., additional, Julia, S., additional, Friedrich, C. C., additional, Keir, S., additional, Saling, J., additional, Roskoski, M., additional, Friedman, H., additional, Bigner, D., additional, Moertel, C., additional, Olin, M., additional, Dahlheimer, T., additional, Gustafson, M., additional, Sumstad, D., additional, McKenna, D., additional, Low, W., additional, Nascene, D., additional, Dietz, A., additional, Ohlfest, J., additional, Sturm, D., additional, Witt, H., additional, Hovestadt, V., additional, Quan, D. A. K., additional, Jones, D. T. W., additional, Konermann, C., additional, Pfaff, E., additional, Korshunov, A., additional, Rizhova, M., additional, Milde, T., additional, Witt, O., additional, Zapatka, M., additional, Collins, V. P., additional, Kool, M., additional, Reifenberger, G., additional, Lichter, P., additional, Lindroth, A. M., additional, Plass, C., additional, Jabado, N., additional, Pfister, S. M., additional, Pizer, B., additional, Salehzadeh, A., additional, Brodbelt, A., additional, Mallucci, C., additional, Brassesco, M., additional, Pezuk, J., additional, Morales, A., additional, de Oliveira, J., additional, Roberto, G., additional, Umezawa, K., additional, Valera, E., additional, Rego, E., additional, Scrideli, C., additional, Tone, L., additional, Veringa, S. J. E., additional, Van Vuurden, D. G., additional, Wesseling, P., additional, Vandertop, W. P., additional, Noske, D. P., additional, Wurdinger, T., additional, Kaspers, G. J. L., additional, Hulleman, E., additional, Wright, K., additional, Broniscer, A., additional, Bendel, A., additional, Bowers, D., additional, Crawford, J., additional, Fisher, P., additional, Hassall, T., additional, Armstrong, G., additional, Baker, J., additional, Qaddoumi, I., additional, Robinson, G., additional, Wetmore, C., additional, Klimo, P., additional, Boop, F., additional, Onar-Thomas, A., additional, Ellison, D., additional, Gajjar, A., additional, Cruz, O., additional, de Torres, C., additional, Sunol, M., additional, Rodriguez, E., additional, Alonso, L., additional, Parareda, A., additional, Cardesa, T., additional, Salvador, H., additional, Celis, V., additional, Guillen, A., additional, Garcia, G., additional, Muchart, J., additional, Trampal, C., additional, Martin, M. L., additional, Rebollo, M., additional, Mora, J., additional, Piotrowski, A., additional, Kowalska, A., additional, Coyle, P., additional, Smith, S., additional, Rogers, H., additional, Macarthur, D., additional, Grundy, R., additional, Puccetti, D., additional, Salamat, S., additional, Kennedy, T., additional, Patel, N., additional, Bradley, K., additional, Casey, K., additional, Iskandar, B., additional, Nakano, Y., additional, Okada, K., additional, Osugi, Y., additional, Yamasaki, K., additional, Fujisaki, H., additional, Fukushima, H., additional, Inoue, T., additional, Matsusaka, Y., additional, Sakamoto, H., additional, Hara, J., additional, De Vleeschouwer, S., additional, Ardon, H., additional, Van Calenbergh, F., additional, Sciot, R., additional, Wilms, G., additional, Van Loon, J., additional, Goffin, J., additional, Van Gool, S., additional, Rusinak, D., additional, Knight, P., additional, Onel, K., additional, Wargowski, D., additional, Stettner, A., additional, Al-Ghafari, A., additional, Punjaruk, W., additional, Coyle, B., additional, Kerr, I., additional, Xipell, E., additional, Rodriguez, M., additional, Gonzalez-Huarriz, M., additional, Tunon, M. T., additional, Zazpe, I., additional, Tejada-Solis, S., additional, Diez-Valle, R., additional, Fueyo, J., additional, Gomez-Manzano, C., additional, Alonso, M. M., additional, Pastakia, D., additional, McCully, C., additional, Murphy, R., additional, Bacher, J., additional, Thomas, M., additional, Steffen-Smith, E., additional, Saleem, K., additional, Waldbridge, S., additional, Widemann, B., additional, Warren, K., additional, Miele, E., additional, Buttarelli, F., additional, Arcella, A., additional, Begalli, F., additional, Po, A., additional, Baldi, C., additional, Carissimo, G., additional, Antonelli, M., additional, Donofrio, V., additional, Morra, I., additional, Nozza, P., additional, Gulino, A., additional, Giangaspero, F., additional, Ferretti, E., additional, Elens, I., additional, Pauwels, F., additional, Fritzell, S., additional, Eberstal, S., additional, Sanden, E., additional, Visse, E., additional, Darabi, A., additional, Siesjo, P., additional, McDonald, P., additional, Wrogemann, J., additional, Krawitz, S., additional, Del Bigio, M., additional, Eisenstat, D., additional, Kwiecien, R., additional, Pietsch, T., additional, Faldum, A., additional, Kortmann, R.-D., additional, Warmuth-Metz, M., additional, Rutkowski, S., additional, Slavc, I., additional, Kramm, C. M., additional, Uparkar, U., additional, Geyer, R., additional, Ermoian, R., additional, Ellenbogen, R., additional, Leary, S., additional, Triscott, J., additional, Hu, K., additional, Fotovati, A., additional, Yip, S., additional, Kast, R., additional, Toyota, B., additional, Dunn, S., additional, Hegde, M., additional, Corder, A., additional, Chow, K., additional, Mukherjee, M., additional, Ashoori, A., additional, Brawley, V., additional, Heslop, H., additional, Gottschalk, S., additional, Yvon, E., additional, Ahmed, N., additional, Wong, T.-T., additional, Yang, F.-Y., additional, Lu, M., additional, Liang, H.-F., additional, Wang, H.-E., additional, Liu, R.-S., additional, Teng, M.-C., additional, Yen, C.-C., additional, Agnihotri, S., additional, Ternamian, C., additional, Jones, C., additional, Zadeh, G., additional, Rutka, J., additional, Hawkins, C., additional, Filipek, I., additional, Drogosiewicz, M., additional, Perek-Polnik, M., additional, Swieszkowska, E., additional, Baginska, B. D., additional, Jurkiewicz, E., additional, Perek, D., additional, Kuehn, A., additional, Falkenstein, F., additional, Gnekow, A., additional, Kramm, C., additional, Brooks, M. D., additional, Jackson, E., additional, Mitra, R. D., additional, Rubin, J. B., additional, Liu, X.-Y., additional, Schwartzentruber, J., additional, Fontebasso, A. M., additional, Quang, D.-A. K., additional, Albrecht, S., additional, Dong, Z., additional, Siegel, P., additional, Von Diemling, A., additional, Faury, D., additional, Tabori, U., additional, Majewski, J., additional, Lulla, R., additional, Echevarria, M., additional, Alden, T., additional, DiPatri, A., additional, Tomita, T., additional, Goldman, S., additional, Lin, T., additional, Merchant, T. E., additional, Kocak, M., additional, Panandiker, A. P., additional, Armstrong, G. T., additional, Gielen, G. H., additional, Muehlen, A. z., additional, Hubert, C., additional, Ding, Y., additional, Toledo, C., additional, Paddison, P., additional, Olson, J., additional, Nandhabalan, M., additional, Bjerke, L., additional, Bax, D., additional, Carvalho, D., additional, Bajrami, I., additional, Ashworth, A., additional, Lord, C., additional, Hargrave, D., additional, Reis, R., additional, Workman, P., additional, Little, S., additional, Popov, S., additional, Jury, A., additional, Burford, A., additional, Doey, L., additional, Al-Sarraj, S., additional, Jurgensmeier, J., additional, Chen, L., additional, Kozarewa, I., additional, Baker, S., additional, Perryman, L., additional, Box, G., additional, Raynaud, F., additional, Eccles, S., additional, Viana-Pereira, M., additional, Pereira, M., additional, Forshew, T., additional, Tatevossian, R., additional, Sheer, D., additional, Pimental, J., additional, Pires, M., additional, Sarkar, C., additional, Jha, P., additional, Patrick, I. R. P., additional, Somasundaram, K., additional, Pathak, P., additional, Sharma, M. C., additional, Suri, V., additional, Suri, A., additional, Gerges, N., additional, Haque, T., additional, Nantel, A., additional, Lee, C., additional, Chen, J., additional, Venugopal, C., additional, Singhal, A., additional, Dunham, C., additional, Kerr, J., additional, Verreault, M., additional, Wakimoto, H., additional, Jayanthan, A., additional, Narendran, A., additional, Singh, S., additional, Giraud, G., additional, Holm, S., additional, Gustavsson, B., additional, Kizyma, R., additional, Kizyma, Z., additional, Dvornyak, L., additional, Kotsay, B., additional, Epari, S., additional, Sharma, P., additional, Gurav, M., additional, Gupta, T., additional, Shetty, P., additional, Moiyadi, A., additional, Kane, S., additional, and Jalali, R., additional

Published
2012
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50. Investigations into the burning-out of organic substances in the ceramic body

Author

Locher, C, Pfaff, E, Schulz, P, and Zografou, C

Subjects
Nonmetallic Materials
Abstract

Pressed compacts were made of spray dried alumina containing water soluble polyvinyl alcohol or cellulose derivative binder. The burning out of organic binder on gradual heating was investigated by visual and microscopic observations of the cross section and by thermogravimetry. Burning out proceeds inward from the peripheries, gradually reducing the size of the black core, which first consists of a dark boundary layer and later turns uniformly black with a sharp boundary. A detailed mechanism of the burning out process between and within the spray dried granules is observed under the microscope. Oxygen atmosphere accelerates the burning out process.

Published
1983

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